Resistance against antimicrobial peptides is independent of Escherichia coli AcrAB, Pseudomonas aeruginosa MexAB and Staphylococcus aureus NorA efflux pumps.
The role of clinically important multidrug resistance (MDR) efflux pumps in bacterial resistance to various human antimicrobial peptides (AMPs), including cathelicidin LL-37, the alpha-defensins human neutrophil peptides (HNPs)-1-3 and HD-5 and the beta-defensins hBD-2 and -3, was investigated. AMP susceptibility testing was performed by killing assays and standard minimal inhibitory concentration assays. AMP susceptibility was determined in Escherichia coli and Pseudomonas aeruginosa strains overexpressing resistance-nodulation-cell division (RND)-type pumps AcrAB and MexAB, respectively, and in their pump-deficient parental strains. Furthermore, the impact of a member of the major facilitator (MF) efflux pump family was investigated in Staphylococcus aureus overexpressing NorA and in wild-type strains. The E. coli AcrAB and P. aeruginosa MexAB RND-type efflux pumps as well as the S. aureus NorA MF efflux pump were unable to confer resistance to AMPs. These findings do not support a critical role of MDR efflux pumps in the tested pathogens as a strategy to increase virulence by circumventing the antimicrobial action of innate defence AMPs.
Rieg
Siegbert
S
Center for Infectious Diseases and Travel Medicine, Department of Medicine, University Hospital, Freiburg, Germany. siegbert.rieg@uniklinik-freiburg.de
Huth
Anja
A
Kalbacher
Hubert
H
Kern
Winfried V
WV
D023181:Antimicrobial Cationic Peptides / Q000494:pharmacology*; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D024881:Drug Resistance, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000096:biosynthesis; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D008074:Lipoproteins / Q000096:biosynthesis; D026901:Membrane Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C083497:AcrA protein, E coli; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; C075040:NorA protein, Staphylococcus